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I thought I would just quickly summarise some of the hits that come up in ChEMBL-NTD for the core structures of the compounds we're working with at the moment. The most active compounds, the "near neighbours", contain both a 2-iminothiazolidinone and 2,5-dialkylpyrrole moiety.

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I have been helping out with public searches for the OSM-S compounds. One of the many utilities of PubChem is as a meta-vendor portal. The question immediately arises as to what analogs of the more potent hits might be available for purchase and testing via the outlinks provided in PubChem. I consider myself able and willing to navigate the bioactivity spaghetti links but this is the first time I have done any serious ferreting through the vendor maze. Because this turned out to be unexpectedly difficult I have written a personal blog post that I hope will be informative for the proje

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One of the most potent compounds identified to date in the OSDD malaria project, the near-neighbour analog OSM-S-35 (ZYH3) was subjected to the hERG assay along with one of the original TCAMS GSK compounds which in this project has the tag OSM-S-5.

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Eight compounds - two GSK originals and 6 promising-looking compounds made during this project were examined by Sue Charman's lab at Monash for metabolic degradation in vivo. In human terms that means they were tested (on a simplistic level) to see whether the compounds would last long in the blood or whether they would likely be metabolised. As part of these studies the solubilities of the compounds were evaluated.

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It is common in drug discovery to have a highly potent hit that has to be optimised to remove undesirable characteristics such as poor oral bioavailablity, metabolic stability or toxicity. In our case, we have a number of highly potent compounds that have quite a high LogP, which is considered a warning sign for both a promiscousity (i.e. binding to many compound targets in vitro) as well as poor oral bioavailabilty (as it breaks the Lipinski Rule of 5).

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There are over 5 million compounds that are available to purchase according to the meta service, E-molecules (http://www.emolecules.com).
It is worth exploring these in the context of the OSDD project as it will identify compound series' that are very easy to explore by purchasing analogues (i.e SAR by catalogue) aswell as identifying compounds that are potentially more sythetically accessible than others (i.e. if there many close neighbours these compounds might be easier to make than others).